TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Tatalović, Nikola
AU  - Brkljačić, Jelena
AU  - Mijović, Milica
AU  - Nestorović, Vojkan
AU  - Mijušković, Ana
AU  - Oreščanin-Dušić, Zorana
AU  - Vidonja Uzelac, Teodora
AU  - Nikolić, Milan
AU  - Spasić, Snežana
AU  - Blagojević, Duško
AU  - Miljević, Čedo
PY  - 2022
UR  - https://www.mdpi.com/1422-0067/23/22/13698
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5344
AB  - Sexual dysfunction, as a noticeable adverse effect of atypical antipsychotic drugs (APDs) for the treatment of schizophrenia, has not been investigated in detail. A study was undertaken to investigate whether 28-day long treatment with clozapine, ziprasidone or sertindole (using a recommended daily dose for atypical antipsychotic therapy), induced histopathological changes both in rat testicles and prostate, changed the activity of the antioxidant defence system and altered blood testosterone and prolactin. Clozapine, ziprasidone and sertindole induced histopathological changes in rat testicular tissue, which could be attributed to a disturbed testicular antioxidant defence system in addition to an altered prolactin to testosterone ratio. None of the APD treatments induced histopathological changes in prostate. Our results demonstrate that APDs have the capacity to change both redox and endocrinological balance. One or both outcomes could underline testicular degeneration and disturbed spermatogenesis.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis
IS  - 22
VL  - 23
DO  - 10.3390/ijms232213698
SP  - 13698
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Tatalović, Nikola and Brkljačić, Jelena and Mijović, Milica and Nestorović, Vojkan and Mijušković, Ana and Oreščanin-Dušić, Zorana and Vidonja Uzelac, Teodora and Nikolić, Milan and Spasić, Snežana and Blagojević, Duško and Miljević, Čedo",
year = "2022",
abstract = "Sexual dysfunction, as a noticeable adverse effect of atypical antipsychotic drugs (APDs) for the treatment of schizophrenia, has not been investigated in detail. A study was undertaken to investigate whether 28-day long treatment with clozapine, ziprasidone or sertindole (using a recommended daily dose for atypical antipsychotic therapy), induced histopathological changes both in rat testicles and prostate, changed the activity of the antioxidant defence system and altered blood testosterone and prolactin. Clozapine, ziprasidone and sertindole induced histopathological changes in rat testicular tissue, which could be attributed to a disturbed testicular antioxidant defence system in addition to an altered prolactin to testosterone ratio. None of the APD treatments induced histopathological changes in prostate. Our results demonstrate that APDs have the capacity to change both redox and endocrinological balance. One or both outcomes could underline testicular degeneration and disturbed spermatogenesis.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis",
number = "22",
volume = "23",
doi = "10.3390/ijms232213698",
pages = "13698"
}

Nikolić-Kokić, A., Tatalović, N., Brkljačić, J., Mijović, M., Nestorović, V., Mijušković, A., Oreščanin-Dušić, Z., Vidonja Uzelac, T., Nikolić, M., Spasić, S., Blagojević, D.,& Miljević, Č.. (2022). Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis. in International Journal of Molecular Sciences
Basel: MDPI., 23(22), 13698.
https://doi.org/10.3390/ijms232213698

Nikolić-Kokić A, Tatalović N, Brkljačić J, Mijović M, Nestorović V, Mijušković A, Oreščanin-Dušić Z, Vidonja Uzelac T, Nikolić M, Spasić S, Blagojević D, Miljević Č. Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis. in International Journal of Molecular Sciences. 2022;23(22):13698.
doi:10.3390/ijms232213698 .

Nikolić-Kokić, Aleksandra, Tatalović, Nikola, Brkljačić, Jelena, Mijović, Milica, Nestorović, Vojkan, Mijušković, Ana, Oreščanin-Dušić, Zorana, Vidonja Uzelac, Teodora, Nikolić, Milan, Spasić, Snežana, Blagojević, Duško, Miljević, Čedo, "Antipsychotic Drug-Mediated Adverse Effects on Rat Testicles May Be Caused by Altered Redox and Hormonal Homeostasis" in International Journal of Molecular Sciences, 23, no. 22 (2022):13698,
https://doi.org/10.3390/ijms232213698 . .

TY  - JOUR
AU  - Oreščanin Dušić, Zorana
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Brkljačić, Jelena
AU  - Nikolić-Kokić, Aleksandra
AU  - Mijušković, Ana
AU  - Spasić, Mihajlo
AU  - Paškulin, Roman
AU  - Bresjanac, Mara
AU  - Blagojević, Duško
PY  - 2018
UR  - https://www.hindawi.com/journals/omcl/2018/5969486/
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2970
AB  - Ibogaine is an indole alkaloid originally extracted from the root bark of the African rainforest shrub Tabernanthe iboga. It has been explored as a treatment for substance abuse because it interrupts drug addiction and relieves withdrawal symptoms. However, it has been shown that ibogaine treatment leads to a sharp and transient fall in cellular ATP level followed by an increase of cellular respiration and ROS production. Since contractile tissues are sensitive to changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated link between altered redox homeostasis and uterine contractile activity. We found that low concentrations of ibogaine stimulated contractile activity in spontaneously active uteri, but incremental increase of doses inhibited it. Inhibitory concentrations of ibogaine led to decreased SOD1 and elevated GSH-Px activity, but doses that completely inhibited contractions increased CAT activity. Western blot analyses showed that changes in enzyme activities were not due to elevated enzyme protein concentrations but posttranslational modifications. Changes in antioxidant enzyme activities point to a vast concentration-dependent increase in H2O2 level. Knowing that extracellular ATP stimulates isolated uterus contractility, while H2O2 has an inhibitory effect, this concentration-dependent stimulation/inhibition could be linked to ibogaine-related alterations in ATP level and redox homeostasis.
T2  - Oxidative Medicine and Cellular Longevity
T1  - The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes
VL  - 2018
DO  - 10.1155/2018/5969486
SP  - 5969486
ER  - 

@article{
author = "Oreščanin Dušić, Zorana and Tatalović, Nikola and Vidonja Uzelac, Teodora and Brkljačić, Jelena and Nikolić-Kokić, Aleksandra and Mijušković, Ana and Spasić, Mihajlo and Paškulin, Roman and Bresjanac, Mara and Blagojević, Duško",
year = "2018",
abstract = "Ibogaine is an indole alkaloid originally extracted from the root bark of the African rainforest shrub Tabernanthe iboga. It has been explored as a treatment for substance abuse because it interrupts drug addiction and relieves withdrawal symptoms. However, it has been shown that ibogaine treatment leads to a sharp and transient fall in cellular ATP level followed by an increase of cellular respiration and ROS production. Since contractile tissues are sensitive to changes in the levels of ATP and ROS, here we investigated an ibogaine-mediated link between altered redox homeostasis and uterine contractile activity. We found that low concentrations of ibogaine stimulated contractile activity in spontaneously active uteri, but incremental increase of doses inhibited it. Inhibitory concentrations of ibogaine led to decreased SOD1 and elevated GSH-Px activity, but doses that completely inhibited contractions increased CAT activity. Western blot analyses showed that changes in enzyme activities were not due to elevated enzyme protein concentrations but posttranslational modifications. Changes in antioxidant enzyme activities point to a vast concentration-dependent increase in H2O2 level. Knowing that extracellular ATP stimulates isolated uterus contractility, while H2O2 has an inhibitory effect, this concentration-dependent stimulation/inhibition could be linked to ibogaine-related alterations in ATP level and redox homeostasis.",
journal = "Oxidative Medicine and Cellular Longevity",
title = "The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes",
volume = "2018",
doi = "10.1155/2018/5969486",
pages = "5969486"
}

Oreščanin Dušić, Z., Tatalović, N., Vidonja Uzelac, T., Brkljačić, J., Nikolić-Kokić, A., Mijušković, A., Spasić, M., Paškulin, R., Bresjanac, M.,& Blagojević, D.. (2018). The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes. in Oxidative Medicine and Cellular Longevity, 2018, 5969486.
https://doi.org/10.1155/2018/5969486

Oreščanin Dušić Z, Tatalović N, Vidonja Uzelac T, Brkljačić J, Nikolić-Kokić A, Mijušković A, Spasić M, Paškulin R, Bresjanac M, Blagojević D. The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes. in Oxidative Medicine and Cellular Longevity. 2018;2018:5969486.
doi:10.1155/2018/5969486 .

Oreščanin Dušić, Zorana, Tatalović, Nikola, Vidonja Uzelac, Teodora, Brkljačić, Jelena, Nikolić-Kokić, Aleksandra, Mijušković, Ana, Spasić, Mihajlo, Paškulin, Roman, Bresjanac, Mara, Blagojević, Duško, "The Effects of Ibogaine on Uterine Smooth Muscle Contractions: Relation to the Activity of Antioxidant Enzymes" in Oxidative Medicine and Cellular Longevity, 2018 (2018):5969486,
https://doi.org/10.1155/2018/5969486 . .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Tatalović, Nikola
AU  - Brkljačić, Jelena
AU  - Mijović, Milica
AU  - Mijušković, Ana
AU  - Miler, Marko
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić, Milan
AU  - Milošević, Verica
AU  - Blagojević, Duško
AU  - Spasić, Mihajlo
AU  - Miljević, Čedo
PY  - 2018
UR  - https://www.tandfonline.com/doi/full/10.1080/15287394.2018.1495587
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3121
AB  - Atypical antipsychotics produce severe side effects including myocarditis that may be attributed to oxidative stress. The aim of this study was to investigate the influence of clozapine, ziprasidone, and sertindole on rat heart morphology and determine whether redox imbalane plays a role in development of histopathological changes. Adult 3-month-old male Wistar rats were treated with recommended daily dose for selected drugs. After 4 week treatment histopathological analysis of the heart was performed and expression and activity of antioxidant enzymes determined. All examined drugs induced histopathological changes that were characterized as toxic myocarditis. Degenerative changes in cardiomyocytes were accompanied by lymphocytic infiltration as well as pericardial histopathological alterations in all treated groups. The least prominent changes were observed in sertindole-treated animals, and most severe with clozapine. Clozapine increased superoxide dismutase 1 (SOD1) activity while ziprasidone reduced glutathione reductase (GR) activity. Sertindole exerted no marked effect on antioxidant enzyme function in the heart even though myocardial degeneration was noted. In conclusion, treatment with clozapine or ziprasidone induced pathophysiological alterations in rat heart, which appeared to be associated disturbances in antioxidant capacity. Abbreviation: AAP, Atypical antipsychotics; ROS, reactive oxygen species; SOD1, Copper-zinc superoxide dismutase; SOD2, Manganese superoxide dismutase; CAT, Catalase; GPx, Glutathione peroxidase; GR, Glutathione reductase; H&E, hematoxylin and eosin stain; TNF- α, tumor necrosis factor alpha.
T2  - Journal of Toxicology and Environmental Health, Part A
T1  - Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function
IS  - 17
VL  - 81
DO  - 10.1080/15287394.2018.1495587
SP  - 844
EP  - 853
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Tatalović, Nikola and Brkljačić, Jelena and Mijović, Milica and Mijušković, Ana and Miler, Marko and Oreščanin Dušić, Zorana and Nikolić, Milan and Milošević, Verica and Blagojević, Duško and Spasić, Mihajlo and Miljević, Čedo",
year = "2018",
abstract = "Atypical antipsychotics produce severe side effects including myocarditis that may be attributed to oxidative stress. The aim of this study was to investigate the influence of clozapine, ziprasidone, and sertindole on rat heart morphology and determine whether redox imbalane plays a role in development of histopathological changes. Adult 3-month-old male Wistar rats were treated with recommended daily dose for selected drugs. After 4 week treatment histopathological analysis of the heart was performed and expression and activity of antioxidant enzymes determined. All examined drugs induced histopathological changes that were characterized as toxic myocarditis. Degenerative changes in cardiomyocytes were accompanied by lymphocytic infiltration as well as pericardial histopathological alterations in all treated groups. The least prominent changes were observed in sertindole-treated animals, and most severe with clozapine. Clozapine increased superoxide dismutase 1 (SOD1) activity while ziprasidone reduced glutathione reductase (GR) activity. Sertindole exerted no marked effect on antioxidant enzyme function in the heart even though myocardial degeneration was noted. In conclusion, treatment with clozapine or ziprasidone induced pathophysiological alterations in rat heart, which appeared to be associated disturbances in antioxidant capacity. Abbreviation: AAP, Atypical antipsychotics; ROS, reactive oxygen species; SOD1, Copper-zinc superoxide dismutase; SOD2, Manganese superoxide dismutase; CAT, Catalase; GPx, Glutathione peroxidase; GR, Glutathione reductase; H&E, hematoxylin and eosin stain; TNF- α, tumor necrosis factor alpha.",
journal = "Journal of Toxicology and Environmental Health, Part A",
title = "Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function",
number = "17",
volume = "81",
doi = "10.1080/15287394.2018.1495587",
pages = "844-853"
}

Nikolić-Kokić, A., Tatalović, N., Brkljačić, J., Mijović, M., Mijušković, A., Miler, M., Oreščanin Dušić, Z., Nikolić, M., Milošević, V., Blagojević, D., Spasić, M.,& Miljević, Č.. (2018). Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function. in Journal of Toxicology and Environmental Health, Part A, 81(17), 844-853.
https://doi.org/10.1080/15287394.2018.1495587

Nikolić-Kokić A, Tatalović N, Brkljačić J, Mijović M, Mijušković A, Miler M, Oreščanin Dušić Z, Nikolić M, Milošević V, Blagojević D, Spasić M, Miljević Č. Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function. in Journal of Toxicology and Environmental Health, Part A. 2018;81(17):844-853.
doi:10.1080/15287394.2018.1495587 .

Nikolić-Kokić, Aleksandra, Tatalović, Nikola, Brkljačić, Jelena, Mijović, Milica, Mijušković, Ana, Miler, Marko, Oreščanin Dušić, Zorana, Nikolić, Milan, Milošević, Verica, Blagojević, Duško, Spasić, Mihajlo, Miljević, Čedo, "Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function" in Journal of Toxicology and Environmental Health, Part A, 81, no. 17 (2018):844-853,
https://doi.org/10.1080/15287394.2018.1495587 . .

TY  - CONF
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Oreščanin Dušić, Zorana
AU  - Brkljačić, Jelena
AU  - Nikolić-Kokić, Aleksandra
AU  - Mijušković, Ana
AU  - Spasić, Mihajlo
AU  - Paškulin, Roman
AU  - Bresjanac, Maja
AU  - Blagojević, Duško
PY  - 2017
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4044
AB  - The ibogaine drug is originated from the rainforest shrub Tabernanthe iboga, which grows in West Africa. The tribes of the Gabon have used the iboga plant root bark as a stimulant, for medicinal purposes, and in rite of passage ceremonies, for centuries. In the western world ibogaine is mostly known for its ability to inspire a sense of wellbeing both mentally and physically. Ibogaine has also been used for the treatment of substance abuse because it interrupts drug addiction, relieves withdrawal symptoms, and significantly decreases the desire for cocaine, heroin, alcohol and most other mind altering drugs. Now it is known that the pharmacology of ibogaine is quite complex and affects many different neurotransmitter systems simultaneously. Ibogaine binds to several types of receptors: 5-Hydroxytryptamine (5-HT), opioid, nicotinic and N-methyl-D-aspartate (NMDA) receptors, dopaminergic and 5-HT transporters and monoamine oxidase enzyme (MAO) 1. Although the mechanisms of ibogaine action in neural tissue are well studied, the effects on peripheral tissues are poorly understood. 
Paskulin et al. have shown that ibogaine causes a sharp and transient fall in cellular ATP level in yeast, which was followed by an immediate increase in respiration and CO2 production, in a time and concentration dependent manner 2, 3. Increased respiration leads to increase of ROS production and subsequent activation of antioxidant enzymes. These effects of ibogaine are not mediated by receptor binding and are not tissue and species specific 2, 4. It was previously shown that ibogaine-induced fall in cellular ATP level was caused by increased ATP consumption. The process in which the consumption of ATP is increased remains unclear. The proteome changes (induction of energy metabolism enzymes, antioxidant enzymes and numerous low abundance proteins) are responsible for at least a part of initial energy expenditures in ibogaine-treated yeast 5, 2. Study on human blood erythrocytes 4 showed that ibogaine leads to release of ATP in the blood plasma. Ibogaine doesn’t have any significant in vitro antioxidant properties per se but it influences physiological oxidative stress defence system in pro-antioxidant manner 3, 4.
In this study, we examined the effects of ibogaine on the model of the isolated rat uterus. Contractile tissues are sensitive to ATP levels and the depletion of energetics could lead to the impairment of regular rhythms and reversible relaxation. Extracellular ATP is known to stimulate uterine contractions in different species but the exact underlying mechanisms are poorly investigated. Furthermore, different contractile tissues, including uterus, are also sensitive to ROS, especially hydrogen peroxide (H2O2) 6. Antioxidant enzyme cytosolic copper-zinc containing superoxide dismutase (SOD1) can also affect the contractility of uterine smooth muscles 7. All these make the isolated contractile tissues a good model for examining the effects of ibogaine on both redox homeostasis and pharmacodinamics.
Unlike isolated arteries and ileum8, the uterus may have a wide range of different types and intensities of contractile activity depending on the properties of the isotonic solution. This allows us to register not only the relaxant but also the stimulatory effect of the tested substance. The aim of this study was to investigate the effects of ibogaine on both contractile properties of uterus and redox homeostasis and explore the possible link between between the two.
Overall, ibogaine treatment has altered redox homeostasis and affected contractile properties of uterus. Ibogaine had the opposite effects on spontaneously active rat uteri depending on the applied concentration. Lower concentrations increased force of contraction, amplitude, frequency and duration of individual contractions. Higher concentrations caused concentration dependent relaxation of spontaneously active uteri. On the other hand, when the uterus is contracting with a high intensity (when exposed to higher Ca2+ concentrations) ibogaine showed only a relaxant effect.
The increase in uterine contractile activity after treatment with low doses of ibogaine could be partly attributed to possible increase in the extracellular concentration of ATP. However, the ATP leads only to a moderate increase in the intensity of uterine contractility, without affecting the character of contractions (i.e. their regularity), whereas ibogaine has a pronounced pace making effect.
Ibogaine also had a concentration dependant effect on the activity of antioxidant enzymes suggesting a vast, increase in cellular respiration and H2O2 level. Ibogaine mediated relaxation found in the present study can be attributed to the influence of H2O2. However, the other possible mechanisms of ibogaine induced smooth muscle relaxation cannot be eliminated, regarding to its wide range of interaction with different receptors and signal transduction pathways.
The results regarding energy metabolism and redox homeostasis are in accordance with the previous observations in different experimental models. Research on an isolated uterus has allowed us to further examine the mechanism of this phenomenon: whether the increase in the intensity of cellular respiration is the result of an increased contractile activity that is caused by ibogaine? Only partially, because ibogaine leads to an increase that is several times greater compared to the uterus with phasic contractile activity of maximal intensity, induced by extracellular Ca2+, indicating the existence of ibogaines tissue non-specific ways of energy metabolism induction.
PB  - Belgrade : Faculty of Chemistry
PB  - Belgrade : Serbian Biochemical Society
C3  - Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings
T1  - The effects of ibogaine on uterine redox homeostasis and contractility
SP  - 203
EP  - 205
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4044
ER  - 

@conference{
author = "Tatalović, Nikola and Vidonja Uzelac, Teodora and Oreščanin Dušić, Zorana and Brkljačić, Jelena and Nikolić-Kokić, Aleksandra and Mijušković, Ana and Spasić, Mihajlo and Paškulin, Roman and Bresjanac, Maja and Blagojević, Duško",
year = "2017",
abstract = "The ibogaine drug is originated from the rainforest shrub Tabernanthe iboga, which grows in West Africa. The tribes of the Gabon have used the iboga plant root bark as a stimulant, for medicinal purposes, and in rite of passage ceremonies, for centuries. In the western world ibogaine is mostly known for its ability to inspire a sense of wellbeing both mentally and physically. Ibogaine has also been used for the treatment of substance abuse because it interrupts drug addiction, relieves withdrawal symptoms, and significantly decreases the desire for cocaine, heroin, alcohol and most other mind altering drugs. Now it is known that the pharmacology of ibogaine is quite complex and affects many different neurotransmitter systems simultaneously. Ibogaine binds to several types of receptors: 5-Hydroxytryptamine (5-HT), opioid, nicotinic and N-methyl-D-aspartate (NMDA) receptors, dopaminergic and 5-HT transporters and monoamine oxidase enzyme (MAO) 1. Although the mechanisms of ibogaine action in neural tissue are well studied, the effects on peripheral tissues are poorly understood. 
Paskulin et al. have shown that ibogaine causes a sharp and transient fall in cellular ATP level in yeast, which was followed by an immediate increase in respiration and CO2 production, in a time and concentration dependent manner 2, 3. Increased respiration leads to increase of ROS production and subsequent activation of antioxidant enzymes. These effects of ibogaine are not mediated by receptor binding and are not tissue and species specific 2, 4. It was previously shown that ibogaine-induced fall in cellular ATP level was caused by increased ATP consumption. The process in which the consumption of ATP is increased remains unclear. The proteome changes (induction of energy metabolism enzymes, antioxidant enzymes and numerous low abundance proteins) are responsible for at least a part of initial energy expenditures in ibogaine-treated yeast 5, 2. Study on human blood erythrocytes 4 showed that ibogaine leads to release of ATP in the blood plasma. Ibogaine doesn’t have any significant in vitro antioxidant properties per se but it influences physiological oxidative stress defence system in pro-antioxidant manner 3, 4.
In this study, we examined the effects of ibogaine on the model of the isolated rat uterus. Contractile tissues are sensitive to ATP levels and the depletion of energetics could lead to the impairment of regular rhythms and reversible relaxation. Extracellular ATP is known to stimulate uterine contractions in different species but the exact underlying mechanisms are poorly investigated. Furthermore, different contractile tissues, including uterus, are also sensitive to ROS, especially hydrogen peroxide (H2O2) 6. Antioxidant enzyme cytosolic copper-zinc containing superoxide dismutase (SOD1) can also affect the contractility of uterine smooth muscles 7. All these make the isolated contractile tissues a good model for examining the effects of ibogaine on both redox homeostasis and pharmacodinamics.
Unlike isolated arteries and ileum8, the uterus may have a wide range of different types and intensities of contractile activity depending on the properties of the isotonic solution. This allows us to register not only the relaxant but also the stimulatory effect of the tested substance. The aim of this study was to investigate the effects of ibogaine on both contractile properties of uterus and redox homeostasis and explore the possible link between between the two.
Overall, ibogaine treatment has altered redox homeostasis and affected contractile properties of uterus. Ibogaine had the opposite effects on spontaneously active rat uteri depending on the applied concentration. Lower concentrations increased force of contraction, amplitude, frequency and duration of individual contractions. Higher concentrations caused concentration dependent relaxation of spontaneously active uteri. On the other hand, when the uterus is contracting with a high intensity (when exposed to higher Ca2+ concentrations) ibogaine showed only a relaxant effect.
The increase in uterine contractile activity after treatment with low doses of ibogaine could be partly attributed to possible increase in the extracellular concentration of ATP. However, the ATP leads only to a moderate increase in the intensity of uterine contractility, without affecting the character of contractions (i.e. their regularity), whereas ibogaine has a pronounced pace making effect.
Ibogaine also had a concentration dependant effect on the activity of antioxidant enzymes suggesting a vast, increase in cellular respiration and H2O2 level. Ibogaine mediated relaxation found in the present study can be attributed to the influence of H2O2. However, the other possible mechanisms of ibogaine induced smooth muscle relaxation cannot be eliminated, regarding to its wide range of interaction with different receptors and signal transduction pathways.
The results regarding energy metabolism and redox homeostasis are in accordance with the previous observations in different experimental models. Research on an isolated uterus has allowed us to further examine the mechanism of this phenomenon: whether the increase in the intensity of cellular respiration is the result of an increased contractile activity that is caused by ibogaine? Only partially, because ibogaine leads to an increase that is several times greater compared to the uterus with phasic contractile activity of maximal intensity, induced by extracellular Ca2+, indicating the existence of ibogaines tissue non-specific ways of energy metabolism induction.",
publisher = "Belgrade : Faculty of Chemistry, Belgrade : Serbian Biochemical Society",
journal = "Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings",
title = "The effects of ibogaine on uterine redox homeostasis and contractility",
pages = "203-205",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4044"
}

Tatalović, N., Vidonja Uzelac, T., Oreščanin Dušić, Z., Brkljačić, J., Nikolić-Kokić, A., Mijušković, A., Spasić, M., Paškulin, R., Bresjanac, M.,& Blagojević, D.. (2017). The effects of ibogaine on uterine redox homeostasis and contractility. in Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings
Belgrade : Faculty of Chemistry., 203-205.
https://hdl.handle.net/21.15107/rcub_ibiss_4044

Tatalović N, Vidonja Uzelac T, Oreščanin Dušić Z, Brkljačić J, Nikolić-Kokić A, Mijušković A, Spasić M, Paškulin R, Bresjanac M, Blagojević D. The effects of ibogaine on uterine redox homeostasis and contractility. in Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings. 2017;:203-205.
https://hdl.handle.net/21.15107/rcub_ibiss_4044 .

Tatalović, Nikola, Vidonja Uzelac, Teodora, Oreščanin Dušić, Zorana, Brkljačić, Jelena, Nikolić-Kokić, Aleksandra, Mijušković, Ana, Spasić, Mihajlo, Paškulin, Roman, Bresjanac, Maja, Blagojević, Duško, "The effects of ibogaine on uterine redox homeostasis and contractility" in Serbian Biochemical Society  Seventh Conference with international participation; Biochemistry of Control in Life and Technology; Proceedings (2017):203-205,
https://hdl.handle.net/21.15107/rcub_ibiss_4044 .

TY  - CONF
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Mijušković, Ana
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasić, Mihajlo
AU  - Bresjanac, Maja
AU  - Paškulin, Roman
AU  - Blagojević, Duško
PY  - 2017
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4279
AB  - The anti-addiction agent ibogaine interacts with different types of neural transmitter receptors, but also decrease cellular ATP level, followed by increased cellular respiration and production
of reactive oxygen species, which change redox homeostasis. We wanted to investigate the effects of single dose of 1 or 20 mg/kg body weight of ibogaine (dose range commonly used for therapeutic
purposes) on activity of antioxidant enzymes (SOD1 and SOD2, catalase - CAT, glutathione peroxidase - GSH-Px, glutathione reductase - GR and glutathione S transferase - GST) in
rat uterus, 6 and 24 h after treatment. Three month-old virgin female rats were treated per os while in estrus phase of estrous cycle (determined by examination of vaginal smear). A problem
in this experimental design was that activity of antioxidant enzymes changes during the estrous cycle (SOD2 activity is lower, GSH-Px and GR activities are higher in estrus compared to
metestrus). Since estrus phase lasts 15–24 h, the female rats treated in estrus, after 6 h will still be in estrus, in most cases, but after 24 h they will be in metestrus. Therefore we used two
approaches for 6 h treatment. First, females were treated immediately upon completion of vaginal smear, and sacrificed 6 h later (in the time of treatment they were in estrus phase). The others
were treated with a delay of 18 h, and sacrificed 6 h later, so that in the time of sacrifice, they were in the same phase as the 24 h group (metestrus). The dose of 20 mg/kg has lowered CAT activity,
but, in general, canonical discriminant analysis shows that the phase of the estrous cycle in the time of sacrifice has a greater impact than a dose of ibogaine. Thus, selection of the phase of
the cycle, appropriate control groups and statistical model are of crucial importance in order to distinguish the effects of treatment from the effects of estrous cycle phase changes.
PB  - Bologna: Federation of European Physiological Societies
C3  - 42nd FEBS Congress, From Molecules to Cells and Back; 2017 Sep 10-14; Jerusalem, Israel
T1  - Determining short-term effects on the activity of antioxidant enzymes in the rat uterus: the example of ibogaine
IS  - Suppl. 1
VL  - 284
DO  - 10.1111/febs.14174
SP  - 233
EP  - 233
ER  - 

@conference{
author = "Tatalović, Nikola and Vidonja Uzelac, Teodora and Mijušković, Ana and Oreščanin Dušić, Zorana and Nikolić-Kokić, Aleksandra and Spasić, Mihajlo and Bresjanac, Maja and Paškulin, Roman and Blagojević, Duško",
year = "2017",
abstract = "The anti-addiction agent ibogaine interacts with different types of neural transmitter receptors, but also decrease cellular ATP level, followed by increased cellular respiration and production
of reactive oxygen species, which change redox homeostasis. We wanted to investigate the effects of single dose of 1 or 20 mg/kg body weight of ibogaine (dose range commonly used for therapeutic
purposes) on activity of antioxidant enzymes (SOD1 and SOD2, catalase - CAT, glutathione peroxidase - GSH-Px, glutathione reductase - GR and glutathione S transferase - GST) in
rat uterus, 6 and 24 h after treatment. Three month-old virgin female rats were treated per os while in estrus phase of estrous cycle (determined by examination of vaginal smear). A problem
in this experimental design was that activity of antioxidant enzymes changes during the estrous cycle (SOD2 activity is lower, GSH-Px and GR activities are higher in estrus compared to
metestrus). Since estrus phase lasts 15–24 h, the female rats treated in estrus, after 6 h will still be in estrus, in most cases, but after 24 h they will be in metestrus. Therefore we used two
approaches for 6 h treatment. First, females were treated immediately upon completion of vaginal smear, and sacrificed 6 h later (in the time of treatment they were in estrus phase). The others
were treated with a delay of 18 h, and sacrificed 6 h later, so that in the time of sacrifice, they were in the same phase as the 24 h group (metestrus). The dose of 20 mg/kg has lowered CAT activity,
but, in general, canonical discriminant analysis shows that the phase of the estrous cycle in the time of sacrifice has a greater impact than a dose of ibogaine. Thus, selection of the phase of
the cycle, appropriate control groups and statistical model are of crucial importance in order to distinguish the effects of treatment from the effects of estrous cycle phase changes.",
publisher = "Bologna: Federation of European Physiological Societies",
journal = "42nd FEBS Congress, From Molecules to Cells and Back; 2017 Sep 10-14; Jerusalem, Israel",
title = "Determining short-term effects on the activity of antioxidant enzymes in the rat uterus: the example of ibogaine",
number = "Suppl. 1",
volume = "284",
doi = "10.1111/febs.14174",
pages = "233-233"
}

Tatalović, N., Vidonja Uzelac, T., Mijušković, A., Oreščanin Dušić, Z., Nikolić-Kokić, A., Spasić, M., Bresjanac, M., Paškulin, R.,& Blagojević, D.. (2017). Determining short-term effects on the activity of antioxidant enzymes in the rat uterus: the example of ibogaine. in 42nd FEBS Congress, From Molecules to Cells and Back; 2017 Sep 10-14; Jerusalem, Israel
Bologna: Federation of European Physiological Societies., 284(Suppl. 1), 233-233.
https://doi.org/10.1111/febs.14174

Tatalović N, Vidonja Uzelac T, Mijušković A, Oreščanin Dušić Z, Nikolić-Kokić A, Spasić M, Bresjanac M, Paškulin R, Blagojević D. Determining short-term effects on the activity of antioxidant enzymes in the rat uterus: the example of ibogaine. in 42nd FEBS Congress, From Molecules to Cells and Back; 2017 Sep 10-14; Jerusalem, Israel. 2017;284(Suppl. 1):233-233.
doi:10.1111/febs.14174 .

Tatalović, Nikola, Vidonja Uzelac, Teodora, Mijušković, Ana, Oreščanin Dušić, Zorana, Nikolić-Kokić, Aleksandra, Spasić, Mihajlo, Bresjanac, Maja, Paškulin, Roman, Blagojević, Duško, "Determining short-term effects on the activity of antioxidant enzymes in the rat uterus: the example of ibogaine" in 42nd FEBS Congress, From Molecules to Cells and Back; 2017 Sep 10-14; Jerusalem, Israel, 284, no. Suppl. 1 (2017):233-233,
https://doi.org/10.1111/febs.14174 . .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Mijušković, Ana
AU  - Tatalović, Nikola
AU  - Brkljačić, Jelena
AU  - Miler, Marko
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić, Milan
AU  - Milošević, Verica
AU  - Blagojević, Duško
AU  - Spasić, Mihajlo
AU  - Miljević, Čedo
PY  - 2016
UR  - https://radar.ibiss.bg.ac.rs/123456789/3900
AB  - The use of atypical antipsychotic drugs (APD) was reported to be associated with adverse effects
on the kidneys. Thus, the aim of this study was to examine whether APD exerted their adverse
effects by interfering with the renal antioxidant defense system. Male 3-mo-old Wistar rats were
treated for 28 d with ziprasidone (ZIP), clozapine (CLO), or sertindole (SER) using a daily dose
recommended for antipsychotic drug therapy. The expression and activities of antioxidant
enzymes superoxide dismutase (SOD) type 1 and type 2, catalase (CAT), glutathione reductase
(GR), and glutathione S-transferases (GSTs) activity were measured in the kidneys. Changes in the
kidneys were also evaluated histologically. Ziprasidone, CLO, and SER reduced renal SOD type 1
and type 2 activities. Decreased CAT activity was observed only in SER-treated rats. An inhibition
in GR activity and increased activity of GST was found only after treatment with CLO. Histological
analysis showed dilatation of proximal tubules in kidneys with all three drugs. In conclusion, data
indicate that redox disturbances may contribute to renal morphologic alterations in proximal
tubules in rats treated with all APD.
PB  - Taylor & Francis
T2  - Journal of Toxicology and Environmental Health, Part A: Current Issues
T1  - Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney
IS  - 20
VL  - 79
DO  - 10.1080/15287394.2016.1201706
SP  - 905
EP  - 911
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Mijušković, Ana and Tatalović, Nikola and Brkljačić, Jelena and Miler, Marko and Oreščanin Dušić, Zorana and Nikolić, Milan and Milošević, Verica and Blagojević, Duško and Spasić, Mihajlo and Miljević, Čedo",
year = "2016",
abstract = "The use of atypical antipsychotic drugs (APD) was reported to be associated with adverse effects
on the kidneys. Thus, the aim of this study was to examine whether APD exerted their adverse
effects by interfering with the renal antioxidant defense system. Male 3-mo-old Wistar rats were
treated for 28 d with ziprasidone (ZIP), clozapine (CLO), or sertindole (SER) using a daily dose
recommended for antipsychotic drug therapy. The expression and activities of antioxidant
enzymes superoxide dismutase (SOD) type 1 and type 2, catalase (CAT), glutathione reductase
(GR), and glutathione S-transferases (GSTs) activity were measured in the kidneys. Changes in the
kidneys were also evaluated histologically. Ziprasidone, CLO, and SER reduced renal SOD type 1
and type 2 activities. Decreased CAT activity was observed only in SER-treated rats. An inhibition
in GR activity and increased activity of GST was found only after treatment with CLO. Histological
analysis showed dilatation of proximal tubules in kidneys with all three drugs. In conclusion, data
indicate that redox disturbances may contribute to renal morphologic alterations in proximal
tubules in rats treated with all APD.",
publisher = "Taylor & Francis",
journal = "Journal of Toxicology and Environmental Health, Part A: Current Issues",
title = "Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney",
number = "20",
volume = "79",
doi = "10.1080/15287394.2016.1201706",
pages = "905-911"
}

Nikolić-Kokić, A., Mijušković, A., Tatalović, N., Brkljačić, J., Miler, M., Oreščanin Dušić, Z., Nikolić, M., Milošević, V., Blagojević, D., Spasić, M.,& Miljević, Č.. (2016). Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney. in Journal of Toxicology and Environmental Health, Part A: Current Issues
Taylor & Francis., 79(20), 905-911.
https://doi.org/10.1080/15287394.2016.1201706

Nikolić-Kokić A, Mijušković A, Tatalović N, Brkljačić J, Miler M, Oreščanin Dušić Z, Nikolić M, Milošević V, Blagojević D, Spasić M, Miljević Č. Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney. in Journal of Toxicology and Environmental Health, Part A: Current Issues. 2016;79(20):905-911.
doi:10.1080/15287394.2016.1201706 .

Nikolić-Kokić, Aleksandra, Mijušković, Ana, Tatalović, Nikola, Brkljačić, Jelena, Miler, Marko, Oreščanin Dušić, Zorana, Nikolić, Milan, Milošević, Verica, Blagojević, Duško, Spasić, Mihajlo, Miljević, Čedo, "Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney" in Journal of Toxicology and Environmental Health, Part A: Current Issues, 79, no. 20 (2016):905-911,
https://doi.org/10.1080/15287394.2016.1201706 . .

TY  - CONF
AU  - Tatalović, Nikola
AU  - Vidonja Uzelac, Teodora
AU  - Mijušković, Ana
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin Dušić, Zorana
AU  - Spasić, Mihajlo
AU  - Paškulin, Roman
AU  - Blagojević, Duško
PY  - 2016
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4203
AB  - The anti-addiction agent ibogaine, prepared from the root of the shrub Tabernanthe iboga and used for the treatment of acute substance abuse, accomplishes its biological effects through interactions with different types of neural transmitter receptors. Ibogaine treatments are sometimes followed by sudden cardiac arrest with a fatal outcome. Ibogaine strongly influences cellular energy, redox state and antioxidant capacity in a dose- and time-dependent manner. Ibogaine application leads to a decrease in cellular ATP level and an increase in CO2 production in the first hour of exposure, followed by increased cellular respiration and production of reactive oxygen species (ROS) which change redox homeostasis after 5 h. It has been proposed that the systemic effect of ibogaine is redox-mediated. In this work, male and female 3 month-old-rats were treated per os with a single dose of either 1 or 20 mg/kg body weight (b.w.) of ibogaine. The activities of antioxidant enzymes: superoxide dismutases 1 and 2 (SOD1 and SOD2, respectively), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S transferase (GST) were measured in the liver, heart and erythrocytes 6 and 24 h after treatment. The treatment with ibogaine did not affect the levels of antioxidants in the liver and erythrocytes in both males and females. However, in males treated with ibogaine, the dose of 1 mg/kg b.w. elevated cardiac MnSOD activity 6 h after administration and lowered it after 24 h. On the other hand, the 20 mg/kg b.w. dose of ibogaine lowered MnSOD and GR activities in the heart 6 and 24 h after administration. In females treated with 20 mg/kg b.w. ibogaine, cardiac SOD and GR activities were lowered. These results suggest that an ibogaine-induced disturbance of ROS homeostasis in the heart is one reason why the heart is more prone to sudden functional disruption and arrest.
PB  - Bratislava, Slovak Republic: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences in cooperation with NO club
C3  - 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts
T1  - Ibogaine affects the redox status in rat heart
SP  - 56
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4203
ER  - 

@conference{
author = "Tatalović, Nikola and Vidonja Uzelac, Teodora and Mijušković, Ana and Nikolić-Kokić, Aleksandra and Oreščanin Dušić, Zorana and Spasić, Mihajlo and Paškulin, Roman and Blagojević, Duško",
year = "2016",
abstract = "The anti-addiction agent ibogaine, prepared from the root of the shrub Tabernanthe iboga and used for the treatment of acute substance abuse, accomplishes its biological effects through interactions with different types of neural transmitter receptors. Ibogaine treatments are sometimes followed by sudden cardiac arrest with a fatal outcome. Ibogaine strongly influences cellular energy, redox state and antioxidant capacity in a dose- and time-dependent manner. Ibogaine application leads to a decrease in cellular ATP level and an increase in CO2 production in the first hour of exposure, followed by increased cellular respiration and production of reactive oxygen species (ROS) which change redox homeostasis after 5 h. It has been proposed that the systemic effect of ibogaine is redox-mediated. In this work, male and female 3 month-old-rats were treated per os with a single dose of either 1 or 20 mg/kg body weight (b.w.) of ibogaine. The activities of antioxidant enzymes: superoxide dismutases 1 and 2 (SOD1 and SOD2, respectively), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S transferase (GST) were measured in the liver, heart and erythrocytes 6 and 24 h after treatment. The treatment with ibogaine did not affect the levels of antioxidants in the liver and erythrocytes in both males and females. However, in males treated with ibogaine, the dose of 1 mg/kg b.w. elevated cardiac MnSOD activity 6 h after administration and lowered it after 24 h. On the other hand, the 20 mg/kg b.w. dose of ibogaine lowered MnSOD and GR activities in the heart 6 and 24 h after administration. In females treated with 20 mg/kg b.w. ibogaine, cardiac SOD and GR activities were lowered. These results suggest that an ibogaine-induced disturbance of ROS homeostasis in the heart is one reason why the heart is more prone to sudden functional disruption and arrest.",
publisher = "Bratislava, Slovak Republic: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences in cooperation with NO club",
journal = "2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts",
title = "Ibogaine affects the redox status in rat heart",
pages = "56",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4203"
}

Tatalović, N., Vidonja Uzelac, T., Mijušković, A., Nikolić-Kokić, A., Oreščanin Dušić, Z., Spasić, M., Paškulin, R.,& Blagojević, D.. (2016). Ibogaine affects the redox status in rat heart. in 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts
Bratislava, Slovak Republic: Institute of Normal and Pathological Physiology, Slovak Academy of Sciences in cooperation with NO club., 56.
https://hdl.handle.net/21.15107/rcub_ibiss_4203

Tatalović N, Vidonja Uzelac T, Mijušković A, Nikolić-Kokić A, Oreščanin Dušić Z, Spasić M, Paškulin R, Blagojević D. Ibogaine affects the redox status in rat heart. in 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts. 2016;:56.
https://hdl.handle.net/21.15107/rcub_ibiss_4203 .

Tatalović, Nikola, Vidonja Uzelac, Teodora, Mijušković, Ana, Nikolić-Kokić, Aleksandra, Oreščanin Dušić, Zorana, Spasić, Mihajlo, Paškulin, Roman, Blagojević, Duško, "Ibogaine affects the redox status in rat heart" in 2nd Joint Meeting of Slovak and Serbian Physiological Societies “Physiology Without Frontiers“, Book of Abstracts (2016):56,
https://hdl.handle.net/21.15107/rcub_ibiss_4203 .

TY  - JOUR
AU  - Nikolić-Kokić, Aleksandra
AU  - Mijušković, Ana
AU  - Tatalović, Nikola
AU  - Brkljačić, Jelena
AU  - Miler, Marko
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić, Milan
AU  - Milošević, Verica
AU  - Blagojević, Duško
AU  - Spasić, Mihajlo
AU  - Miljević, Čedo
PY  - 2016
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4042
AB  - The use of atypical antipsychotic drugs (APD) was reported to be associated with adverse effectson the kidneys. Thus, the aim of this study was to examine whether APD exerted their adverseeffects by interfering with the renal antioxidant defense system. Male 3-mo-old Wistar rats weretreated for 28 d with ziprasidone (ZIP), clozapine (CLO), or sertindole (SER) using a daily doserecommended for antipsychotic drug therapy. The expression and activities of antioxidantenzymes superoxide dismutase (SOD) type 1 and type 2, catalase (CAT), glutathione reductase(GR), and glutathione S-transferases (GSTs) activity were measured in the kidneys. Changes in thekidneys were also evaluated histologically. Ziprasidone, CLO, and SER reduced renal SOD type 1and type 2 activities. Decreased CAT activity was observed only in SER-treated rats. An inhibitionin GR activity and increased activity of GST was found only after treatment with CLO. Histologicalanalysis showed dilatation of proximal tubules in kidneys with all three drugs. In conclusion, dataindicate that redox disturbances may contribute to renal morphologic alterations in proximaltubules in rats treated with all APD.
PB  - Taylor & Francis
T2  - Journal of Toxicology and Environmental Health, Part A: Current Issues
T1  - Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney
IS  - 20
VL  - 79
DO  - 10.1080/15287394.2016.1201706
SP  - 905
EP  - 911
ER  - 

@article{
author = "Nikolić-Kokić, Aleksandra and Mijušković, Ana and Tatalović, Nikola and Brkljačić, Jelena and Miler, Marko and Oreščanin Dušić, Zorana and Nikolić, Milan and Milošević, Verica and Blagojević, Duško and Spasić, Mihajlo and Miljević, Čedo",
year = "2016",
abstract = "The use of atypical antipsychotic drugs (APD) was reported to be associated with adverse effectson the kidneys. Thus, the aim of this study was to examine whether APD exerted their adverseeffects by interfering with the renal antioxidant defense system. Male 3-mo-old Wistar rats weretreated for 28 d with ziprasidone (ZIP), clozapine (CLO), or sertindole (SER) using a daily doserecommended for antipsychotic drug therapy. The expression and activities of antioxidantenzymes superoxide dismutase (SOD) type 1 and type 2, catalase (CAT), glutathione reductase(GR), and glutathione S-transferases (GSTs) activity were measured in the kidneys. Changes in thekidneys were also evaluated histologically. Ziprasidone, CLO, and SER reduced renal SOD type 1and type 2 activities. Decreased CAT activity was observed only in SER-treated rats. An inhibitionin GR activity and increased activity of GST was found only after treatment with CLO. Histologicalanalysis showed dilatation of proximal tubules in kidneys with all three drugs. In conclusion, dataindicate that redox disturbances may contribute to renal morphologic alterations in proximaltubules in rats treated with all APD.",
publisher = "Taylor & Francis",
journal = "Journal of Toxicology and Environmental Health, Part A: Current Issues",
title = "Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney",
number = "20",
volume = "79",
doi = "10.1080/15287394.2016.1201706",
pages = "905-911"
}

Nikolić-Kokić, A., Mijušković, A., Tatalović, N., Brkljačić, J., Miler, M., Oreščanin Dušić, Z., Nikolić, M., Milošević, V., Blagojević, D., Spasić, M.,& Miljević, Č.. (2016). Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney. in Journal of Toxicology and Environmental Health, Part A: Current Issues
Taylor & Francis., 79(20), 905-911.
https://doi.org/10.1080/15287394.2016.1201706

Nikolić-Kokić A, Mijušković A, Tatalović N, Brkljačić J, Miler M, Oreščanin Dušić Z, Nikolić M, Milošević V, Blagojević D, Spasić M, Miljević Č. Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney. in Journal of Toxicology and Environmental Health, Part A: Current Issues. 2016;79(20):905-911.
doi:10.1080/15287394.2016.1201706 .

Nikolić-Kokić, Aleksandra, Mijušković, Ana, Tatalović, Nikola, Brkljačić, Jelena, Miler, Marko, Oreščanin Dušić, Zorana, Nikolić, Milan, Milošević, Verica, Blagojević, Duško, Spasić, Mihajlo, Miljević, Čedo, "Effects of antipsychotic drug administration on antioxidative defense enzymes in male rat kidney" in Journal of Toxicology and Environmental Health, Part A: Current Issues, 79, no. 20 (2016):905-911,
https://doi.org/10.1080/15287394.2016.1201706 . .

TY  - CONF
AU  - Mijušković, Ana
AU  - Tatalović, Nikola
AU  - Nikolić-Kokić, Aleksandra
AU  - Oreščanin Dušić, Zorana
AU  - Spasić, Mihajlo
AU  - Blagojević, Duško
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4043
AB  - The uterus is a spontaneously active tissue, whose contractions have to be controlled and
regulated for successful pregnancy and parturition. Spontaneous contractions might be initiated
by spontaneous pacemaker activity, although pacemaker cells are not fully defined. Myometrial
membrane potential changes are essential for uterine activity which is a function of ion movement
across the membrane governed by ion channel activity [1]. Changes in membrane potential are
achieved by coordinated actions of two classes of channels: those that exert hyperpolarizing
current and those that exert depolarizing currents. Calcium-activated chloride channels (CaCCs)
are important contributors to depolarizing currents 1,2. However, the molecular identity of CaCCs
is still not known. Several candidates have been proposed including bestrophins (BEST), CLCA
and the anoctamin (ANO or TMEM) family of proteins 3.
Improper or irregular uterine activity may underlie the common pathological disorders such
as infertility, improper implantation, dysmenorrhea, weak uterine contraction during labor and
preterm labor. The contractile activity of the uterus is regulated by the complex electrophysiologic
network which is highly sensitive to various pharmacological and signaling molecules.
Hydrogen sulphide (H2S) appears to be an important signaling molecule in rat uterus. The
production of H2S and the presence of enzymes responsible for its endogenous production
(cystathionine beta-synthase and cystathionine gamma-lyase) have been demonstrated in rat
uterus 3,4. Hydrogen sulphide reduces uterine contractility, and it is recognized as a promising
treatment for uterine disorders. It decreases amplitude as well as frequency of uterine
contractions. H2S effect on the frequency of contractions appears to be mediated via pacemaker
channels. CaCCs channel inhibitors were shown to reduce the frequency of spontaneous
contractions in myometrial strips and were proposed to be the main pacemaker channels in
smooth muscles 1. Very little, however, is known about these channels in the myometrium.
The mechanism of the H2S -induced relaxation in non-pregnant uteri has not been examined.
Organ bath studies were employed to assess the pharmacological effects of sodium sulphide
(Na2S; hydrogen sulphide donor) in uterine strips by exposing them to Na2S with or without
Cl− channel blockers (DIDS, NFA, T16Ainh-A01, TA). Relaxation was not affected by
majority of CaCC modulators since T16Ainh-AO1, tannic acid and NFA failed to inhibit
Na2S induced relaxation but is DIDS sensitive 3. DIDS was recently found to be highly
selective for bestrophin (BEST-1) channels 5.
BEST proteins were shown to recapitulate the properties of native CaCCs. Although
both bestrophin and calcium-activated chloride channel families were proposed to be the
candidate genes for smooth muscle contraction their exact function and regulation remain
to be confirmed 6.
The aim of this study was to explore the expression of bestrophins channels (BEST-1
and BEST-2) in rat uterus in estrus. Expression studies of the BEST-1 and BEST-2 were
performed by Western blotting, RT-PCR and immunohistochemistry. BEST-1 and BEST-2
are expresses at the mRNA level and at protein level in rat uterus in estrus, suggesting a role
for BESTs in the control of uterine contractility. However, expression of BEST-1 is higher
comparing to BEST-2. Moreover, BEST-1 seems to be major mediators of Na2S induced
uterine relaxation. Mechanistic insights of possible Na2S-induced modulation od BEST-1
were performed by molecular docking studies.
Taken together, work undertaken strengthens the evidence of a physiologically important
role for bestrophin channels in the normal physiology of uterine contractions. Moreover, is
an important modulator of uterine contractions and bestrophins appear to be main modulator
of its effects. This research add to our understanding of molecular mechanisms of H2S effects
and will be beneficial in designing future in vivo studies, and ultimately identifying new
therapeutic targets to treat uterine disorders that are associated with disturbed contractility.
PB  - Belgrade : Faculty of Chemistry
PB  - Belgrade : Serbian Biochemical Society
C3  - Serbian Biochemical Society  Fifth Conference; Integrated research in life science; Proceedings
T1  - Calcium-activated chloride channels and Na2S-induced relaxation of non-pregnant rat uteri in estrus
SP  - 111
EP  - 112
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4043
ER  - 

@conference{
author = "Mijušković, Ana and Tatalović, Nikola and Nikolić-Kokić, Aleksandra and Oreščanin Dušić, Zorana and Spasić, Mihajlo and Blagojević, Duško",
year = "2015",
abstract = "The uterus is a spontaneously active tissue, whose contractions have to be controlled and
regulated for successful pregnancy and parturition. Spontaneous contractions might be initiated
by spontaneous pacemaker activity, although pacemaker cells are not fully defined. Myometrial
membrane potential changes are essential for uterine activity which is a function of ion movement
across the membrane governed by ion channel activity [1]. Changes in membrane potential are
achieved by coordinated actions of two classes of channels: those that exert hyperpolarizing
current and those that exert depolarizing currents. Calcium-activated chloride channels (CaCCs)
are important contributors to depolarizing currents 1,2. However, the molecular identity of CaCCs
is still not known. Several candidates have been proposed including bestrophins (BEST), CLCA
and the anoctamin (ANO or TMEM) family of proteins 3.
Improper or irregular uterine activity may underlie the common pathological disorders such
as infertility, improper implantation, dysmenorrhea, weak uterine contraction during labor and
preterm labor. The contractile activity of the uterus is regulated by the complex electrophysiologic
network which is highly sensitive to various pharmacological and signaling molecules.
Hydrogen sulphide (H2S) appears to be an important signaling molecule in rat uterus. The
production of H2S and the presence of enzymes responsible for its endogenous production
(cystathionine beta-synthase and cystathionine gamma-lyase) have been demonstrated in rat
uterus 3,4. Hydrogen sulphide reduces uterine contractility, and it is recognized as a promising
treatment for uterine disorders. It decreases amplitude as well as frequency of uterine
contractions. H2S effect on the frequency of contractions appears to be mediated via pacemaker
channels. CaCCs channel inhibitors were shown to reduce the frequency of spontaneous
contractions in myometrial strips and were proposed to be the main pacemaker channels in
smooth muscles 1. Very little, however, is known about these channels in the myometrium.
The mechanism of the H2S -induced relaxation in non-pregnant uteri has not been examined.
Organ bath studies were employed to assess the pharmacological effects of sodium sulphide
(Na2S; hydrogen sulphide donor) in uterine strips by exposing them to Na2S with or without
Cl− channel blockers (DIDS, NFA, T16Ainh-A01, TA). Relaxation was not affected by
majority of CaCC modulators since T16Ainh-AO1, tannic acid and NFA failed to inhibit
Na2S induced relaxation but is DIDS sensitive 3. DIDS was recently found to be highly
selective for bestrophin (BEST-1) channels 5.
BEST proteins were shown to recapitulate the properties of native CaCCs. Although
both bestrophin and calcium-activated chloride channel families were proposed to be the
candidate genes for smooth muscle contraction their exact function and regulation remain
to be confirmed 6.
The aim of this study was to explore the expression of bestrophins channels (BEST-1
and BEST-2) in rat uterus in estrus. Expression studies of the BEST-1 and BEST-2 were
performed by Western blotting, RT-PCR and immunohistochemistry. BEST-1 and BEST-2
are expresses at the mRNA level and at protein level in rat uterus in estrus, suggesting a role
for BESTs in the control of uterine contractility. However, expression of BEST-1 is higher
comparing to BEST-2. Moreover, BEST-1 seems to be major mediators of Na2S induced
uterine relaxation. Mechanistic insights of possible Na2S-induced modulation od BEST-1
were performed by molecular docking studies.
Taken together, work undertaken strengthens the evidence of a physiologically important
role for bestrophin channels in the normal physiology of uterine contractions. Moreover, is
an important modulator of uterine contractions and bestrophins appear to be main modulator
of its effects. This research add to our understanding of molecular mechanisms of H2S effects
and will be beneficial in designing future in vivo studies, and ultimately identifying new
therapeutic targets to treat uterine disorders that are associated with disturbed contractility.",
publisher = "Belgrade : Faculty of Chemistry, Belgrade : Serbian Biochemical Society",
journal = "Serbian Biochemical Society  Fifth Conference; Integrated research in life science; Proceedings",
title = "Calcium-activated chloride channels and Na2S-induced relaxation of non-pregnant rat uteri in estrus",
pages = "111-112",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4043"
}

Mijušković, A., Tatalović, N., Nikolić-Kokić, A., Oreščanin Dušić, Z., Spasić, M.,& Blagojević, D.. (2015). Calcium-activated chloride channels and Na2S-induced relaxation of non-pregnant rat uteri in estrus. in Serbian Biochemical Society  Fifth Conference; Integrated research in life science; Proceedings
Belgrade : Faculty of Chemistry., 111-112.
https://hdl.handle.net/21.15107/rcub_ibiss_4043

Mijušković A, Tatalović N, Nikolić-Kokić A, Oreščanin Dušić Z, Spasić M, Blagojević D. Calcium-activated chloride channels and Na2S-induced relaxation of non-pregnant rat uteri in estrus. in Serbian Biochemical Society  Fifth Conference; Integrated research in life science; Proceedings. 2015;:111-112.
https://hdl.handle.net/21.15107/rcub_ibiss_4043 .

Mijušković, Ana, Tatalović, Nikola, Nikolić-Kokić, Aleksandra, Oreščanin Dušić, Zorana, Spasić, Mihajlo, Blagojević, Duško, "Calcium-activated chloride channels and Na2S-induced relaxation of non-pregnant rat uteri in estrus" in Serbian Biochemical Society  Fifth Conference; Integrated research in life science; Proceedings (2015):111-112,
https://hdl.handle.net/21.15107/rcub_ibiss_4043 .

TY  - CONF
AU  - Tatalović, Nikola
AU  - Bajrica, Mina
AU  - Mijušković, Ana
AU  - Oreščanin Dušić, Zorana
AU  - Nikolić-Kokić, Aleksandra
AU  - Spasić, Mihajlo
AU  - Blagojević, Duško
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4202
AB  - Ibogaine is a naturally occurring alkaloid isolated from the bark of the roots of the West African Tabernanthe iboga plant. It’s well known for its anti-addictive effects. On the other hand, pharmacology is quite complex, affecting many different neurotransmitter systems simultaneously. Ibogaine binds to several types of receptors: 5-Hydroxytryptamine (5-HT), opioid, nicotinic and N-methyl-D-aspartate (NMDA) receptors, dopaminergic and 5-HT transporters and monoamine oxidase enzyme (MAO). Based on our previous study showing ibogaine effects on ATP liberation (127 pM) from erythrocites in vitro, we wanted to investigate direct pharmacological ibogaine effects on aorta and mesenteric artery and to compare them with effects of ATP. Its effects were tested by isolated organ bath studies using aorta and mesenteric artery rings (with and without endothelium) isolated from Wistar rats. Aortic and mesenteric artery rings were precontracted with phenylephrine (10 µM). Ibogaine (64.4 µM) produced a relaxation in the aortic as well as in mesenteric artery rings, in a similar way. Realaxation effects were followed in time (5, 10, 20, 30, and 60 minutes) and it was shown that ibogaine effects are time-dependent. In addition, ibogaine effects are also endothelium dependent since presence of endothelium facilitated relaxation. ATP (127 pM) induced relaxation in the aortic as well as in mesenteric artery rings, and this effect is completely endothelium dependent. Taken together these findings suggest that ibogaine affect smooth muscles directly. Additionally, relaxation is endothelium dependent (possibly is mediated via nitric oxide) and ATP-mediated.
PB  - Ljubljana, Slovenia: Slovenian Biochemical Society
C3  - FEBS3+ Meeting, Molecules of Life, Book of Abstracts
T1  - Ibogaine relaxes rat arteries: the role of endothelium
SP  - 194
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4202
ER  - 

@conference{
author = "Tatalović, Nikola and Bajrica, Mina and Mijušković, Ana and Oreščanin Dušić, Zorana and Nikolić-Kokić, Aleksandra and Spasić, Mihajlo and Blagojević, Duško",
year = "2015",
abstract = "Ibogaine is a naturally occurring alkaloid isolated from the bark of the roots of the West African Tabernanthe iboga plant. It’s well known for its anti-addictive effects. On the other hand, pharmacology is quite complex, affecting many different neurotransmitter systems simultaneously. Ibogaine binds to several types of receptors: 5-Hydroxytryptamine (5-HT), opioid, nicotinic and N-methyl-D-aspartate (NMDA) receptors, dopaminergic and 5-HT transporters and monoamine oxidase enzyme (MAO). Based on our previous study showing ibogaine effects on ATP liberation (127 pM) from erythrocites in vitro, we wanted to investigate direct pharmacological ibogaine effects on aorta and mesenteric artery and to compare them with effects of ATP. Its effects were tested by isolated organ bath studies using aorta and mesenteric artery rings (with and without endothelium) isolated from Wistar rats. Aortic and mesenteric artery rings were precontracted with phenylephrine (10 µM). Ibogaine (64.4 µM) produced a relaxation in the aortic as well as in mesenteric artery rings, in a similar way. Realaxation effects were followed in time (5, 10, 20, 30, and 60 minutes) and it was shown that ibogaine effects are time-dependent. In addition, ibogaine effects are also endothelium dependent since presence of endothelium facilitated relaxation. ATP (127 pM) induced relaxation in the aortic as well as in mesenteric artery rings, and this effect is completely endothelium dependent. Taken together these findings suggest that ibogaine affect smooth muscles directly. Additionally, relaxation is endothelium dependent (possibly is mediated via nitric oxide) and ATP-mediated.",
publisher = "Ljubljana, Slovenia: Slovenian Biochemical Society",
journal = "FEBS3+ Meeting, Molecules of Life, Book of Abstracts",
title = "Ibogaine relaxes rat arteries: the role of endothelium",
pages = "194",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4202"
}

Tatalović, N., Bajrica, M., Mijušković, A., Oreščanin Dušić, Z., Nikolić-Kokić, A., Spasić, M.,& Blagojević, D.. (2015). Ibogaine relaxes rat arteries: the role of endothelium. in FEBS3+ Meeting, Molecules of Life, Book of Abstracts
Ljubljana, Slovenia: Slovenian Biochemical Society., 194.
https://hdl.handle.net/21.15107/rcub_ibiss_4202

Tatalović N, Bajrica M, Mijušković A, Oreščanin Dušić Z, Nikolić-Kokić A, Spasić M, Blagojević D. Ibogaine relaxes rat arteries: the role of endothelium. in FEBS3+ Meeting, Molecules of Life, Book of Abstracts. 2015;:194.
https://hdl.handle.net/21.15107/rcub_ibiss_4202 .

Tatalović, Nikola, Bajrica, Mina, Mijušković, Ana, Oreščanin Dušić, Zorana, Nikolić-Kokić, Aleksandra, Spasić, Mihajlo, Blagojević, Duško, "Ibogaine relaxes rat arteries: the role of endothelium" in FEBS3+ Meeting, Molecules of Life, Book of Abstracts (2015):194,
https://hdl.handle.net/21.15107/rcub_ibiss_4202 .

TY  - THES
AU  - Mijušković, Ana
PY  - 2015
UR  - http://eteze.bg.ac.rs/application/showtheses?thesesId=3022
UR  - https://fedorabg.bg.ac.rs/fedora/get/o:11254/bdef:Content/download
UR  - http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=47664911
UR  - http://nardus.mpn.gov.rs/123456789/5637
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2438
AB  - Kontrakcije uterusa su važne za regulaciju brojnih reproduktivnihfunkcija. Neregularna i neadekvatna aktivnost uterusa povezana je sa brojnimpatološkim stanjima: neplodnost, neadekavtna implantacija, dismenoreja, kasnetrudnoće i prevremeni porođaji. Kontraktilnost uterusa regulisana jekompleksnom elektrofiziološkom mrežom koja može biti modulirana različitimfarmakološkim i signalnim molekulima.Uterus se karakteriše izuzetnom osobinom, brzom adaptacijom iz stanjamirovanja u oscilatorne cikluse jakih kontrakcija. Ovo je omogućeno zahvaljujućiaktivnosti ćelija koje su sposobne da remodeliraju svoje signalne puteve.Endogeno-sintetisani vodonik-sulfid (H2S), koji je zajedno sa azotmonoksidomi ugljen-monoksidom prepoznat kao gasoviti transmiter, imasignalnu ulogu i u uterusu. Vodonik-sulfid redukuje kontrakcije uterusa iprepoznat je kao agens velikog potencijala u tretmanu oboljenja uterusa. Do sadanisu urađene detaljnije studije, koje su dale uvid u mehanizme njegovogrelaksantnog dejstva na uterusu, te je to od značajnog interesa. Nije poznatoda li subiološki efekti sulfida posredovani njegovim molekulskim oblikom (H2S) ilitiolatnim anjonom (HS−).Rezultati ove disertacije implicirali su da molekulska i anjonska forma nemogu imati identične farmakološke efekte, uključujući i regulaciju konraktilnosti.Efekti H2S/HS− na relaksaciju uterusa upoređeni su sa efektom metantiol (CH3SH,koji „imitira“ H2S). Uočene razlike mogu biti posljedica specifične aktivnosti HS−jona. Ujedno, ovo upoređivanje može biti jedan od načina za razlikovanje efekataH2S i HS−. Metabolizam CH3SH je povezan sa sulfidom, budući da se H2S metiluje doCH3SH i ova metilacija može biti novi način modulacije H2S efekata in vivo.Ispitivano je učešće jonskih kanala (K+, Ca2+, Cl−), kao posrednika u relaksacijiuterusa indukovanoj sa H2S/HS−. Nađeno je da sulfid izaziva reverzibilnukoncentracijski-zavisnu relaksaciju koja je posredovana DIDS-osjetljivim Cl−kanalom. Dodatno, pokazano je da je DIDS-osjetljivi CaCC kanal (engl. Ca2+-...
AB  - Uterine contractions are important in many reproductive functions.Improper or irregular uterine activity may underlie the common pathologicaldisorders such as infertility, improper implantation, dysmenorrhea, weak uterinecontraction during labor and preterm labor. The contractile activity of the uterus isregulated by the complex electrophysiologic network which is highly sensitive tovarious pharmacological and signaling molecules. Remarkably, uterus is able toswitch from quiescence to oscillatory cycles of strong contractions. This isdependent on the activity of the cells being able to remodel their signallingsystems.Endogenously produced hydrogen sulphide (H2S), which, together withNO and CO, is a recognized gasotransmitter, also appears to be a signallingmolecule in rat uterus. Hydrogen sulphide reduces uterine contractility, and it isrecognized as a promising treatment for uterine disorders. There were no studiesabout mechanistic insights of its relaxatory effect, done so far, and thus is ofpotential interest. It is not currently known whether the biological effects of H2Sare mediated directly by H2S or by its derivatives, the most important being thethiolate anion HS−. The results presented in this thesis imply that it appearsunlikely that molecular and anionic forms have pharmacologically identicalactions, including the regulation of contractility. Pharmacological effects ofH2S/HS− were compared to effects of methanethiol (CH3SH, mimicks H2S), andobserved differences might be a consequence of the specific actions of HS−. Thiscomparison may represent a useful tool for discrimination between differentactions of H2S and HS−. The metabolism of CH3SH is intertwined with hydrogensulfide (H2S), since the later is methylated to CH3SH and this methylation may be anew way of modulation of H2S effects in vivo.We investigated the involvement of ion channels (K+, Ca2+, Cl−) in therelaxation of rat uteri induced by H2S/HS−. We found that sulphide induces...
PB  - Belgrade: University of Belgrade, Faculty of Chemistry
T2  - University of Belgrade, Faculty of Chemistry
T1  - Mehanizmi relaksantnog efekta natrijum-sulfida na uterus pacova in vitro: efektorne vrste i ciljne molekulske strukture
T1  - Mechanisms of sodium sulphide relaxatory effect in rat uterus in vitro: reactive species and molecular targets
SP  - 1
EP  - 161
UR  - https://hdl.handle.net/21.15107/rcub_nardus_5637
ER  - 

@phdthesis{
author = "Mijušković, Ana",
year = "2015",
abstract = "Kontrakcije uterusa su važne za regulaciju brojnih reproduktivnihfunkcija. Neregularna i neadekvatna aktivnost uterusa povezana je sa brojnimpatološkim stanjima: neplodnost, neadekavtna implantacija, dismenoreja, kasnetrudnoće i prevremeni porođaji. Kontraktilnost uterusa regulisana jekompleksnom elektrofiziološkom mrežom koja može biti modulirana različitimfarmakološkim i signalnim molekulima.Uterus se karakteriše izuzetnom osobinom, brzom adaptacijom iz stanjamirovanja u oscilatorne cikluse jakih kontrakcija. Ovo je omogućeno zahvaljujućiaktivnosti ćelija koje su sposobne da remodeliraju svoje signalne puteve.Endogeno-sintetisani vodonik-sulfid (H2S), koji je zajedno sa azotmonoksidomi ugljen-monoksidom prepoznat kao gasoviti transmiter, imasignalnu ulogu i u uterusu. Vodonik-sulfid redukuje kontrakcije uterusa iprepoznat je kao agens velikog potencijala u tretmanu oboljenja uterusa. Do sadanisu urađene detaljnije studije, koje su dale uvid u mehanizme njegovogrelaksantnog dejstva na uterusu, te je to od značajnog interesa. Nije poznatoda li subiološki efekti sulfida posredovani njegovim molekulskim oblikom (H2S) ilitiolatnim anjonom (HS−).Rezultati ove disertacije implicirali su da molekulska i anjonska forma nemogu imati identične farmakološke efekte, uključujući i regulaciju konraktilnosti.Efekti H2S/HS− na relaksaciju uterusa upoređeni su sa efektom metantiol (CH3SH,koji „imitira“ H2S). Uočene razlike mogu biti posljedica specifične aktivnosti HS−jona. Ujedno, ovo upoređivanje može biti jedan od načina za razlikovanje efekataH2S i HS−. Metabolizam CH3SH je povezan sa sulfidom, budući da se H2S metiluje doCH3SH i ova metilacija može biti novi način modulacije H2S efekata in vivo.Ispitivano je učešće jonskih kanala (K+, Ca2+, Cl−), kao posrednika u relaksacijiuterusa indukovanoj sa H2S/HS−. Nađeno je da sulfid izaziva reverzibilnukoncentracijski-zavisnu relaksaciju koja je posredovana DIDS-osjetljivim Cl−kanalom. Dodatno, pokazano je da je DIDS-osjetljivi CaCC kanal (engl. Ca2+-..., Uterine contractions are important in many reproductive functions.Improper or irregular uterine activity may underlie the common pathologicaldisorders such as infertility, improper implantation, dysmenorrhea, weak uterinecontraction during labor and preterm labor. The contractile activity of the uterus isregulated by the complex electrophysiologic network which is highly sensitive tovarious pharmacological and signaling molecules. Remarkably, uterus is able toswitch from quiescence to oscillatory cycles of strong contractions. This isdependent on the activity of the cells being able to remodel their signallingsystems.Endogenously produced hydrogen sulphide (H2S), which, together withNO and CO, is a recognized gasotransmitter, also appears to be a signallingmolecule in rat uterus. Hydrogen sulphide reduces uterine contractility, and it isrecognized as a promising treatment for uterine disorders. There were no studiesabout mechanistic insights of its relaxatory effect, done so far, and thus is ofpotential interest. It is not currently known whether the biological effects of H2Sare mediated directly by H2S or by its derivatives, the most important being thethiolate anion HS−. The results presented in this thesis imply that it appearsunlikely that molecular and anionic forms have pharmacologically identicalactions, including the regulation of contractility. Pharmacological effects ofH2S/HS− were compared to effects of methanethiol (CH3SH, mimicks H2S), andobserved differences might be a consequence of the specific actions of HS−. Thiscomparison may represent a useful tool for discrimination between differentactions of H2S and HS−. The metabolism of CH3SH is intertwined with hydrogensulfide (H2S), since the later is methylated to CH3SH and this methylation may be anew way of modulation of H2S effects in vivo.We investigated the involvement of ion channels (K+, Ca2+, Cl−) in therelaxation of rat uteri induced by H2S/HS−. We found that sulphide induces...",
publisher = "Belgrade: University of Belgrade, Faculty of Chemistry",
journal = "University of Belgrade, Faculty of Chemistry",
title = "Mehanizmi relaksantnog efekta natrijum-sulfida na uterus pacova in vitro: efektorne vrste i ciljne molekulske strukture, Mechanisms of sodium sulphide relaxatory effect in rat uterus in vitro: reactive species and molecular targets",
pages = "1-161",
url = "https://hdl.handle.net/21.15107/rcub_nardus_5637"
}

Mijušković, A.. (2015). Mehanizmi relaksantnog efekta natrijum-sulfida na uterus pacova in vitro: efektorne vrste i ciljne molekulske strukture. in University of Belgrade, Faculty of Chemistry
Belgrade: University of Belgrade, Faculty of Chemistry., 1-161.
https://hdl.handle.net/21.15107/rcub_nardus_5637

Mijušković A. Mehanizmi relaksantnog efekta natrijum-sulfida na uterus pacova in vitro: efektorne vrste i ciljne molekulske strukture. in University of Belgrade, Faculty of Chemistry. 2015;:1-161.
https://hdl.handle.net/21.15107/rcub_nardus_5637 .

Mijušković, Ana, "Mehanizmi relaksantnog efekta natrijum-sulfida na uterus pacova in vitro: efektorne vrste i ciljne molekulske strukture" in University of Belgrade, Faculty of Chemistry (2015):1-161,
https://hdl.handle.net/21.15107/rcub_nardus_5637 .

TY  - JOUR
AU  - Filipović, Milos R
AU  - Eberhardt, Mirjam
AU  - Prokopović, Vladimir
AU  - Mijušković, Ana
AU  - Reeh, Peter
AU  - Oreščanin Dušić, Zorana
AU  - Ivanović-Burmazović, Ivana S
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1041
AB  - Hydrogen sulfide (H2S) has been increasingly recognized as an important signaling molecule that regulates both blood pressure and neuronal activity. Attention has been drawn to its interactions with another gasotransmitter, nitric oxide (NO). Here, we provide evidence that the physiological effects observed upon the application of sodium nitroprusside (SNP) and H2S can be ascribed to the generation of nitroxyl (HNO), which is a direct product of the reaction between SNP and H2S, not a consequence of released NO subsequently reacting with H2S. Intracellular HNO formation has been confirmed, and the subsequent release of calcitonin gene related peptide from a mouse heart has been demonstrated. Unlike with other thiols, SNP reacts with H2S in the same way as rhodanese, i.e, the cyanide transforms into a thiocyanate. These findings shed new light on how H2S is understood to interact with nitroprusside. Additionally, they offer a new and convenient pharmacological source of HNO for therapeutic purposes.
T2  - Journal of Medicinal Chemistry
T1  - Beyond H2S and NO Interplay: Hydrogen Sulfide and Nitroprusside React Directly to Give Nitroxyl (HNO). A New Pharmacological Source of HNO
IS  - 4
VL  - 56
DO  - 10.1021/jm3012036
SP  - 793
EP  - 1508
ER  - 

@article{
author = "Filipović, Milos R and Eberhardt, Mirjam and Prokopović, Vladimir and Mijušković, Ana and Reeh, Peter and Oreščanin Dušić, Zorana and Ivanović-Burmazović, Ivana S",
year = "2013",
abstract = "Hydrogen sulfide (H2S) has been increasingly recognized as an important signaling molecule that regulates both blood pressure and neuronal activity. Attention has been drawn to its interactions with another gasotransmitter, nitric oxide (NO). Here, we provide evidence that the physiological effects observed upon the application of sodium nitroprusside (SNP) and H2S can be ascribed to the generation of nitroxyl (HNO), which is a direct product of the reaction between SNP and H2S, not a consequence of released NO subsequently reacting with H2S. Intracellular HNO formation has been confirmed, and the subsequent release of calcitonin gene related peptide from a mouse heart has been demonstrated. Unlike with other thiols, SNP reacts with H2S in the same way as rhodanese, i.e, the cyanide transforms into a thiocyanate. These findings shed new light on how H2S is understood to interact with nitroprusside. Additionally, they offer a new and convenient pharmacological source of HNO for therapeutic purposes.",
journal = "Journal of Medicinal Chemistry",
title = "Beyond H2S and NO Interplay: Hydrogen Sulfide and Nitroprusside React Directly to Give Nitroxyl (HNO). A New Pharmacological Source of HNO",
number = "4",
volume = "56",
doi = "10.1021/jm3012036",
pages = "793-1508"
}

Filipović, M. R., Eberhardt, M., Prokopović, V., Mijušković, A., Reeh, P., Oreščanin Dušić, Z.,& Ivanović-Burmazović, I. S.. (2013). Beyond H2S and NO Interplay: Hydrogen Sulfide and Nitroprusside React Directly to Give Nitroxyl (HNO). A New Pharmacological Source of HNO. in Journal of Medicinal Chemistry, 56(4), 793-1508.
https://doi.org/10.1021/jm3012036

Filipović MR, Eberhardt M, Prokopović V, Mijušković A, Reeh P, Oreščanin Dušić Z, Ivanović-Burmazović IS. Beyond H2S and NO Interplay: Hydrogen Sulfide and Nitroprusside React Directly to Give Nitroxyl (HNO). A New Pharmacological Source of HNO. in Journal of Medicinal Chemistry. 2013;56(4):793-1508.
doi:10.1021/jm3012036 .

Filipović, Milos R, Eberhardt, Mirjam, Prokopović, Vladimir, Mijušković, Ana, Reeh, Peter, Oreščanin Dušić, Zorana, Ivanović-Burmazović, Ivana S, "Beyond H2S and NO Interplay: Hydrogen Sulfide and Nitroprusside React Directly to Give Nitroxyl (HNO). A New Pharmacological Source of HNO" in Journal of Medicinal Chemistry, 56, no. 4 (2013):793-1508,
https://doi.org/10.1021/jm3012036 . .

TY  - CONF
AU  - Mijušković, Ana
AU  - Dusić, ZO
AU  - Nikolić-Kokić, Aleksandra
AU  - Slavić, Marija
AU  - Milovanović, S
AU  - Blagojević, Duško
AU  - Spasić, Mihajlo
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/987
C3  - Febs Journal
T1  - An investigation of the mechanism of hydrogen sulphide mediated uterine relaxation
IS  - null
VL  - 280
SP  - 5
EP  - 185
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_987
ER  - 

@conference{
author = "Mijušković, Ana and Dusić, ZO and Nikolić-Kokić, Aleksandra and Slavić, Marija and Milovanović, S and Blagojević, Duško and Spasić, Mihajlo",
year = "2013",
journal = "Febs Journal",
title = "An investigation of the mechanism of hydrogen sulphide mediated uterine relaxation",
number = "null",
volume = "280",
pages = "5-185",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_987"
}

Mijušković, A., Dusić, Z., Nikolić-Kokić, A., Slavić, M., Milovanović, S., Blagojević, D.,& Spasić, M.. (2013). An investigation of the mechanism of hydrogen sulphide mediated uterine relaxation. in Febs Journal, 280(null), 5-185.
https://hdl.handle.net/21.15107/rcub_ibiss_987

Mijušković A, Dusić Z, Nikolić-Kokić A, Slavić M, Milovanović S, Blagojević D, Spasić M. An investigation of the mechanism of hydrogen sulphide mediated uterine relaxation. in Febs Journal. 2013;280(null):5-185.
https://hdl.handle.net/21.15107/rcub_ibiss_987 .

Mijušković, Ana, Dusić, ZO, Nikolić-Kokić, Aleksandra, Slavić, Marija, Milovanović, S, Blagojević, Duško, Spasić, Mihajlo, "An investigation of the mechanism of hydrogen sulphide mediated uterine relaxation" in Febs Journal, 280, no. null (2013):5-185,
https://hdl.handle.net/21.15107/rcub_ibiss_987 .